Molecular Design of Oncolytic Adenoviruses

This chapter aims to review different genetic modifications that have been used to design tumor-selective (“oncolytic”) adenoviruses. Other nongenetic modifications have been used to improve the antitumor properties of adenoviruses, such as pegylation of the capsid and nonviral delivery of infectious genomes, but these are not in the scope of this chapter. The methods to construct recombinant adenoviruses are presented elsewhere in this book. The chapter explains genetic modifications to achieve tumor-selective replication, to increase oncolytic potency, the insertion of transgenes, and finally, genetic modification of the capsid for tumor targeting and epitope display. The nucleotide positions or insertions or deletions commonly used in the design of oncolytic adenoviruses are indicated based on the human adenovirus type 5 reference material, GenBank Accession Number AY339865.